Methods of treating premalignant and malignant growths of the skin have often been traumatic. A common method of treating disorders such as actinic keratosis has been the application of liquid nitrogen to destroy the affected tissue. Epidermal tumors are commonly treated by physical removal through surgery. A method which has been used in the past is chemosurgery through the application of escharotic or fixative chemicals such as zinc chloride. This method has not been found to be particularly effective because of the physical discomfort associated with the use of such materials. It also has the disadvantage of destroying both healthy tissue and the diseased tissue. Neither has the use of known antitumor drugs been found to be particularly effective in the treatment of skin tumors since these drugs are commonly applied systemically resulting in substantial side effects due to their toxicity.
The naturally occurring meso form of the catecholic butane, nordihydroguaiaretic acid [meso-1,4-bis (3,4-dihydroxyphenyl)-2,3-dimethylbutane] ("NDGA") is found in the creosote bush, and its general structure (generic to all of its stereoisomeric forms) is given in Formula (I). ##STR1## The creosote bush was used for centuries to brew a tea which was the basis for a folk remedy that called for drinking the tea to cure colds, rheumatism and other ailments. However, this remedy has not proven to be successful. NDGA was also used for years as an antioxidant to inhibit the development of rancidity in the fats of food products and as a stabilizer of pharmaceutical preparations, perfumary oils, rubber and other industrial products.
C. R. Smart et al. in the Rocky Mountain Medical Journal, Nov. 1970, pp. 39-43, conducted clinical studies to ascertain the validity of an earlier report of tumor regression in a melanoma of a patient taking "Chaparrel Tea", which contains NDGA. In the clinical study conducted by Smart et al., human cancer patients ingested either "Chapparrel Tea", an aqueous extract of Larrea divericata containing NDGA, or doses of pure NDGA. Although some positive results were observed, the authors advised against treatment with "Chaparrel Tea" due to a significant number of reported cases of tumor stimulation. This confirmed the earlier screening studies of NDGA conducted by Leiter et al. of the Cancer Chemotherapy National Service Center of the National Cancer Institute, which obtained negative results when NDGA was tested against several types of cancer cells.
Surprisingly, it has now been discovered that catecholic butanes, particularly nordihydroguaiaretic acid, and/or derivatives thereof as defined herein, in a pharmaceutical composition, are effective in treating benign, premalignant and malignant growths, preferably when directly applied to the situs, without the detrimental side effects associated with chemotherapy or chemosurgical techniques. The compositions provide particularly advantageous results when applied topically to the afflicted area of the skin, or injected into the growth. As disclosed in copending application Ser. Nos. 699,923 and 924,620, such compositions are also effective in treating disorders of the skin including acne and psoriasis, in aiding in the healing of skin wounds and in alleviating bacterial, viral and fungal infections when applied to the situs of the disorder. The compositions are also useful in the treatment of warts.